MOLECULAR-BASIS AND EXPRESSION OF THE LW(A)/LW(B) BLOOD-GROUP POLYMORPHISM

The Landsteiner-Wiener (LW) blood group antigens reside on a 42-kD erythrocyte membrane glycoprotein that has recently been cloned. Here, we found that the molecular basis for the LW(a)/LW(b) polymorphism is determined by a single base pair mutation (A308G) that correlates with a Pvu II restriction site and results in a Gln70Arg amino acid substitution. COS-7 cells transfected with LW(a) or LW(b) cDNAs reacted with human anti-LM(a) and anti-LW(b) sera, respectively, as well as with a murine monoclonal anti-LW(ab) antibody, as shown by flow cytometry analysis. Moreover, a 42-kD protein was immunoprecipitated from the transfected cells with the monoclonal anti-LW(ab) antibody. These findings indicate that LW(a) and LW(b) are alleles of the LW blood group locus as defined also by a monoclonal anti-LW(ab) of nonhuman origin, in addition, the LW locus has been assigned to chromosome 19p13.3 by in situ hybridization. Study by Southern blot analysis indicated also that the LW locus is composed of a single gene that was not grossly rearranged in rare LW(a-b-) and Rh-null individuals deficient for LW antigens. In addition, Pvu II restriction fragment-length polymorphism analysis indicated that these variants were all homozygous for a phenotypically silent LM(a) allele. (C) 1995 by The American Society of Hematology.